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Published on: March 30, 2019
Inhibition of farnesyltransferase reduces angiogenesis by interrupting endothelial cell migration
Guoyuan Peng1, Yuan Ren, Xiaodong Sun
1State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Abstract:
Inhibitors of farnesyltransferase (FTI) have been developed for cancer treatment for more than a decade. Aside from being a therapeutic target in tumor cells, little is known about the role of farnesyltransferase (FTase) in other physiological processes. In this study, we revealed the involvement of FTase in angiogenesis and showed that FTI inhibited angiogenesis by directly acting on endothelial cells. Inhibition of FTase interrupted cell migration in vitro and in vivo. In addition, we found that FTase was important for cell polarization, cell spreading and pseudopodia formation. We also found that FTase interacted with microtubule end binding protein 1 (EB1) and that this interaction was critical for the localization of EB1 to microtubule tips. Our findings thus offer novel insight into the functions of FTase in endothelial cells and provide valuable information for the use of FTI in cancer therapy.
Insights
Farnesyltransferase inhibitors (FTI) block angiogenesis by targeting endothelial cells, impacting cell migration, polarization, and interaction with microtubule end binding protein 1 (EB1). This reveals new functions for farnesyltransferase (FTase) in cancer therapy.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Farnesyltransferase inhibitors (FTI) are explored for cancer treatment.
- The physiological roles of farnesyltransferase (FTase) beyond tumor cells are not well understood.
Purpose of the Study:
- To investigate the role of FTase in angiogenesis.
- To determine the mechanism by which FTIs affect endothelial cells.
Main Methods:
- In vitro and in vivo assays to assess cell migration.
- Analysis of cell polarization, spreading, and pseudopodia formation.
- Co-immunoprecipitation to study protein interactions.
Main Results:
- FTase is involved in angiogenesis, and FTIs inhibit this process by directly acting on endothelial cells.
- FTase inhibition disrupts endothelial cell migration, polarization, spreading, and pseudopodia formation.
- FTase interacts with microtubule end binding protein 1 (EB1), crucial for EB1's localization to microtubule tips.
Conclusions:
- FTase plays a significant role in endothelial cell function and angiogenesis.
- FTIs offer a potential therapeutic strategy for inhibiting angiogenesis in cancer.
- The interaction between FTase and EB1 provides novel insights into FTase's cellular functions.
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